Expression of K-Ras, p53 and Ki-67 in Precancerous and Cancerous Lesions of Colorectum.

The immunological assessment at molecular profiling of K-Ras, p53 and Ki-67 along with EGFR, BRAF and others like BCL-2 has been the focus of several workers. The incidence of colorectal adenomatous polyp with dysplastic changes and colorectal carcinoma per se in the context of Indian population as per the ICMR registry, New Delhi, India, is significant. We wanted to study precancerous lesions (adenoma, polyp) and adenocarcinoma of colorectum for the expression of K-Ras, p53 and Ki-67 in biopsy or surgical specimen of colon by immunohistochemistry for its occurrence. We also wanted to study the intratumor heterogeneity of aforesaid expression for the purposes of prognostication and correlation with other clinicopathological parameters. MethodsThis is a cross sectional study conducted in the Surgical Pathology and Division of Immunohistochemistry, Department of Pathology, Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, Maharashtra, India, for a duration of 2 years. Total seventy patients of all ages and genders suspected of 1) precancerous lesions of adenomas and polyps (35 cases) and 2) adenocarcinoma on colonoscopic biopsy or surgical specimens (35 cases) were included in the study. The expression of K-Ras, p53 and Ki-67 as primary objectives along with EGFR, BRAF and others like BCL-2 as secondary objectives were recorded, tabulated and compared for the purposes of predictive parameters in colorectal neoplastic lesions. ResultsMost of the cases of CRC were over the age of 50 years and Male:Female ratio was 5:3.Twenty-five cases of group 2 (CRC) showed positive IHC for K-Ras. p53 was detected in 28 cases and high Ki-67 index was observed in all 32 cases of CRC. The comparative statistics in the pilot study showed that the immunoexpression of K-Ras, p53 and Ki-67 is significantly higher in group 2 (CRC) compared to cases in group 1 (polyps) and group 3 (normal). ConclusionsExpression of K-Ras, p53 and Ki-67 is likely to be the distinguishing tissue biomarkers between benign and malignant colorectal disease process as well as have prognostic and predictive value in colorectal cancer. The addition of EGFR, BRAF and BCL-2 would help in determining the pathogenesis and offer targeted therapeutic intervention.

Clinical Significance of Signet-Ring-Cell Colorectal Cancer as a Prognostic Factor

PURPOSE: The aim of this study is to evaluate the prognosis for patients with a signet-ring-cell carcinoma (SRCC) who undergo curative surgery by comparing them to patients with an adenocarcinoma (ADC), excluding a mucinous ADC. METHODS: Between September 1994 and December 2013, 14,110 patients with colorectal cancer underwent surgery and among them, 12,631 patients were enrolled in this study. 71 patients with a SRCC and 12,570 patients with a ADC were identified. We analyzed the disease-free survival and the overall survival rates before and after a 1:2 propensity score matching and evaluated those rates after stage stratification. RESULTS: The median follow-up durations were 48.5 months for the SRC group and 48.6 months for the ADC group. The disease-free survival rates and the overall survival rates were significantly lower in the SRC group before and after propensity score matching (P < 0.001). After stratification by stage, no differences were observed between the SRC and the ADC groups for the disease-free survival (DFS) and the overall survival (OS) rates for patients with cancer in its early stages (P = 0.913 and P = 0.380 for the DFS and the OS, respectively, in stages 0 and I, and P = 0.223 and P = 0.991 for the DFS and the OS, respectively, in stage II), but those rates were significantly lower in the SRC group for cancer in its later stages (P < 0.001, respectively in stages III and IV). CONCLUSION: For cancer in advanced stages, patients with a resectable colorectal SRCC had a poorer prognosis after propensity score matching than those with an ADC did. Therefore, more intensive surveillance and closer observation should be offered to such patients.

Application of Integrative Medicines of TCM and WM Combined with Fast-track Surgery Concept in Perioperative Nursing in Colorectal Surgery / 昆明医科大学学报

Objective To study the clinical effect and significance of integrative medicines of TCM and WM combined with fast-track surgery concept on perioperative nursing in colorectal surgery.Methods One hundred and twenty patients with surgery were randomly divided into the observation group and the control group,60 cases in each group.The control group was treated with conventional nursing,while the observation group was treated with fast track surgery nursing of integrative medicines of TCM and WM.Results Bowel sound recovery time,anus exhaust time,defecation time,length of hospital stay and postoperative complications of observation group was significantly less than the control group (P＜0.05).Nursing total satisfaction of observation group was significantly higher than the control group (P＜0.05).Conclusion Integrative medicines of TCM and WM combined with fast-track surgery concept on perioperative nursing in colorectal surgery can reduce stress,speed up the recovery,reduce complications.So it is a safe and effective way of perioperative nursing,and worthy of clinical popularization and application.

Increasing cancer incidence in a tertiary care hospital in a developing country, India.

OBJECTIVE: Cancer is a major health problem in many countries including India. Since Cancer Registries are incomplete in India, only a few epidemiological studies have been done so far. The objective was to determine the leading causes of cancer in a tertiary care hospital and compare the incidences of different types of cancer with the incidences in India and developed countries. MATERIALS AND METHODS: An epidemiological study was done to collect data from pathology records of 1003 cancer cases during 6‑month period in the year 2010. The data was collected in a computer and the data was utilized to make tables and histograms. RESULTS: Of the 1003 cases, the leading cancer site was breast, followed by colon and rectum, lymph node and stomach. The leading cancer site for men was colon and rectum and for women was breast. CONCLUSION: Cancer incidence is now low in India, a developing country, compared to developed Western countries. However, some cancers, like breast and colon and rectum cancers are increasing every year. IMPACT: The findings of this study support that cancer incidence is increasing in India and more epidemiological studies are needed.

Endoscopic submucosal dissection for colorectal lesions in elderly patients / 中华消化内镜杂志

Objective To investigate the safety and effectiveness of endoscopic submucosal dissection(ESD)for elderly patients(≥60 years old)with colorectal lesions.Methods Data of 31 elderly patients(≥60 years old)and 23 non-elderly(0.05 ). Thirty-two lesions in elderly group and twenty-five lesions in non-elderly group were all curative resection.En bloc resection rates were 96.9%(31 /32)and 96.0%(24 /25)in the elderly group and non-elderly group respectively;the rates of bleeding during ESD procedure were 3.2%(1 /31 )and 4.3%(1 /23);delayed bleeding rates were 12.9%(4 /31)and 13.0%(3 /23);the rates of perforation was 12.9%(4 /31)and 0;postoperative infection rates were 3.2%(1 /31)and 4.3%(1 /23)respectively.There were no statistical differences between the two groups in any of these data (P >0.05 ).The mean time of follow-up were (14.8 ±1.7)months in elderly group and (14.7 ±1.8)months in non-elderly group,and there was no significant difference between two groups.No residual lesion or recurrent lesion was found in the follow-up period.Conclusion ESD is a safe and effective treatment for the elderly patients with colorectal lesion.

Colorectal Subepithelial Lesions

Most of subepithelial lesion (SEL) being identified was accidentally discovered as small bulging lesion covered with normal mucosa from endoscopic screening. The type of treatment and prognosis vary depending on the type of tumor, it would be crucial to perform an accurate differential diagnosis. Since the differentiation of SEL relied on the indirect findings observed from the mucosal surface using an endoscopy only in the past, it was able to confirm the presence of lesion only but difficult to identify complex detailed nature of the lesion. However, after the endoscopic ultrasonography (EUS) was introduced, it became possible to identify extrinsic compression, and size of intramural tumors, internal properties and contour so that it gets possible to have differential diagnosis of lesions and prediction on the lesion whether it is malignant or benign. In addition, the use of EUS-guided fine needle aspiration and EUS-guided core biopsy made it possible to make histological differential diagnosis. This study intended to investigate endoscopic and EUS findings, histological diagnosis, treatment regimen and impression of colorectal SELs.

Endoscopic and pathological features of colorectal serrated adenoma: comparison with traditional adenoma / 中华消化内镜杂志

Objective To analyze the differences in endoscopic and pathological features between colorectal serrated adenoma (SA) and colorectal traditional adenoma.Methods The endoscopic and pathological features of 80 cases of SA and 160 cases of traditional adenoma diagnosed from June 2008 to October 2013 were retrospectively analyzed.Results The SA patients were younger than the traditional adenoma patients (57.5 VS 62.3,P =0.003 8).The lesions of SA were mostly located in rectosigmoid colon (60％),while the traditional adenoma could be found in rectosigmoid colon (45％),ascending colon (20％) and descending colon (19％).There were significant differences in the lesion's location between two kinds of adenoma (P ＜ 0.05).There were no differences in gender,the size of lesion or endoscopic classification.In terms of the pathological features,SA had the serrated structure,whereas tubular,tubulovillous and villous structure were found in traditional adenoma.Cancer could be found in 1.9％ of SA,which was lower than that of traditional adenoma (P ＜ 0.05).Conclusion Serrated adenoma is different from traditional adenoma on the patient's age,lesion's location and pathological features.It is an unique kind of adenoma with potential malignancy,which should be emphasized in clinical practice.

Diminutive and Small Colorectal Polyps: The Pathologist's Perspective

Recent progress in advanced endoscopic imaging and electronic chromoendoscopy allows the real-time endoscopic estimation of the histologic type of polyps, mainly for the differentiation of adenomas from hyperplastic polyps. Accordingly, a "resect-and-discard" strategy applied to diminutive colorectal polyps is now one of the emerging issues among gastroenterologists. The strategy has a practical advantage in terms of the potential cost savings. However, it has a number of limitations in the medical, academic, and legal aspects. The major pitfalls include the endoscopic investigation of colorectal polyps with a wide variety of histogenetic origins, including serrated polyps, and the lack of a standardized method for polyp size measurement. Another issue is the importance of the pathologic diagnosis for legal purposes and medical research. Moreover, it is not certain whether the implementation of the strategy has economic benefit in countries with an undervalued reimbursement system for pathologic examination. There is no doubt that a highly confident optical diagnosis of polyp type is a novel valuable tool. It can provide a more steady symbiosis between gastroenterologists and pathologists to allow a more evident diagnosis and management of patients with colorectal polyps.

The Impact of Mechanical Bowel Preparation in Elective Colorectal Surgery: A Propensity Score Matching Analysis

PURPOSE: To evaluate the influence of preoperative mechanical bowel preparation (MBP) based on the occurrence of anastomosis leakage, surgical site infection (SSI), and severity of surgical complication when performing elective colorectal surgery. MATERIALS AND METHODS: MBP and non-MBP patients were matched using propensity score. The outcomes were evaluated according to tumor location such as right- (n=84) and left-sided colon (n=50) and rectum (n=100). In the non-MBP group, patients with right-sided colon cancer did not receive any preparation, and patients with both left-sided colon and rectal cancers were given one rectal enema before surgery. RESULTS: In the right-sided colon surgery, there was no anastomosis leakage. SSI occurred in 2 (4.8%) and 4 patients (9.5%) in the non-MBP and MBP groups, respectively. In the left-sided colon cancer surgery, there was one anastomosis leakage (4.0%) in each group. SSI occurred in none in the rectal enema group and in 2 patients (8.0%) in the MBP group. In the rectal cancer surgery, there were 5 anastomosis leakages (10.0%) in the rectal enema group and 2 (4.0%) in the MBP group. SSI occurred in 3 patients (6.0%) in each groups. Severe surgical complications (Grade III, IV, or V) based on Dindo-Clavien classification, occurred in 7 patients (14.0%) in the rectal enema group and 1 patient (2.0%) in the MBP group (p=0.03). CONCLUSION: Right- and left-sided colon cancer surgery can be performed safely without MBP. In rectal cancer surgery, rectal enema only before surgery seems to be dangerous because of the higher rate of severe postoperative complications.

Indications for and Technical Aspects of Colorectal Endoscopic Submucosal Dissection

Due to the widespread acceptance of gastric and esophageal endoscopic submucosal dissections (ESDs), the number of medical facilities that perform colorectal ESDs has grown and the effectiveness of colorectal ESD has been increasingly reported in recent years. The clinical indications for colorectal ESD at the National Cancer Center Hospital, Tokyo, Japan include laterally spreading tumor (LST) nongranular type lesions >20 mm and LST granular type lesions >30 mm. In addition, 0-IIc lesions >20 mm, intramucosal tumors with nonlifting signs and large sessile lesions, all of which are difficult to resect en bloc by conventional endoscopic mucosal resection (EMR), represent potential candidates for colorectal ESD. Rectal carcinoid tumors less than 1 cm in diameter can be treated simply, safely, and effectively by endoscopic submucosal resection using a ligation device and are therefore not indications for ESD. The en bloc resection rate was 90%, and the curative resection rate was 87% for 806 ESDs. The median procedure time was 60 minutes, and the mean size for resected specimens was 40 mm (range, 15 to 150 mm). Perforations occurred in 23 (2.8%) cases, and postoperative bleeding occurred in 15 (1.9%) cases, but only two perforation cases required emergency surgery (0.25%). ESD was an effective procedure for treating colorectal tumors that are difficult to resect en bloc by conventional EMR. ESD resulted in a higher en bloc resection rate as well as decreased invasiveness in comparison to surgery. Based on the excellent clinical results of colorectal ESDs in Japan, the Japanese healthcare insurance system has approved colorectal ESD for coverage.

SSTR2A Protein Expression in Neuroendocrine Neoplasms of the Colorectum

BACKGROUND: Expression studies of somatostatin receptor type 2A (SSTR2A) in neuroendocrine neoplasms (NENs) led to the development of clinically relevant diagnostic and therapeutic strategies. However, most of these strategies used in-house-developed antibodies and were focused on lung tumors. We evaluated commercially available SSTR2A antibodies in NENs of the colorectum to observe their subcellular localization and distribution within the resected tumor. METHODS: The immunohistochemistry of 77 NENs located in the colorectum were studied using a commercially available antibody against SSTR2A. RESULTS: Most neuroendocrine tumors (NET) grade (G)1 and G2 expressed the SSTR2A in the cytoplasm with apical or luminal localization. However, all neuroendocrine carcinomas (NEC) G3 were negative for SSTR2A. CONCLUSIONS: Our data indicate that SSTR2A immunohistochemistry shows cytoplasmic staining with distinct subcellular localization in most NET G1 in the colorectum using a commercially available antibody. Low or no expression of SSTR2A in NET G2 and NEC G3 raises the possibility that SSTR2A may correlate with histologic differentiation and proliferative activity. Further validation studies in large case series are needed.

Clinicopathologic Analysis of Gastrointestinal Stromal Tumors of the Colon and Rectum

PURPOSE: This study's aim is to investigate the clinicopathologic characteristics of colorectal gastrointestinal stromal tumors (GISTs) and to evaluate the result of those tumors. METHODS: We retrospectively reviewed 22 patients who had been diagnosed with primary colorectal GISTs and who had undergone a surgical resection between October 1996 and July 2008. RESULTS: Colorectal GISTs accounted for 0.28% of all colorectal malignancies and 7.7% of all GISTs. Rectal GISTs (19, 86.4%) were more common than colonic GISTs (3, 13.6%). According to the National Institute of Health's (NIH) grading system, there were 1 (4.5%) very low, 5 (22.7%) low, 4 (18.2%) intermediate, and 12 (54.6%) high-risk tumors. The disease recurred in 7 patients (1 with intermediate risk and 6 with high risk). Recurrence sites were the liver (42.9%), the peritoneum (71.5%), and the lymph nodes (14.3%). Adjuvant imatinib therapy and/or radiation therapy were done for patients with microscopically positive margins of resection and high risk, of which one experienced a recurrence at 95 months after surgery. The five-year recurrence rates were 0% in the very-low-grade and low-grade groups, 33.3% in the intermediate-grade group, and 37.5% in the high-grade group. The five-year overall survival rates were 100% in the very-low-grade and low-grade groups, 66.7% in the intermediate-grade group, and 62.5% in the high-grade group. CONCLUSION: Poor prognosis of colorectal GISTs was closely related to the tumor's histologic grade and size. Integrating surgery, molecular therapy, and radiation therapy might improve outcomes, but further study with more cases is needed.

Expression of MUC2 and MUC6 in Colorectal Adenomas and Adenocarcinomas

PURPOSE: Although the expression of MUC2 is seen in colorectal tumors, there have been few reports about the expression of MUC6 in colorectal tumors. The aim of this study was to investigate the expressions of MUC2 and MUC6 in normal colorectal tissues and in tumors, as well as the association of MUC2 and MUC6 expressions with prognostic factors. METHODS: Twenty (20) cases of colorectal adenomas treated by using a endoscopic polypectomy and 30 cases of colorectal carcinomas treated by using a resection were collected. Ten (10) normal tissue samples were obtained apart from the carcinomas. Sections were used for MUC2 and MUC6 immunostaining. The expressions of MUC2 and MUC6 were scored by using the sum of the percentages of the stained cells and the intensity of staining. RESULTS: All of the ten normal colorectal tissues expressed MUC2 and MUC6. Of the 20 adenomas, 19 cases (95%) were MUC2 positive, and 17 cases (85%) were MUC6 positive. Adenomas with severe atypia tended to express lower levels of MUC2 and MUC6 than those with mild or moderate atypia. Of the 30 carcinomas, 28 cases (93%) were MUC2 positive and 19 cases (63.3%) were MUC6 positive. Colorectal mucinous carcinomas differed significantly from non-mucinous carcinomas in strong MUC6 expression. MUC2 expression showed a significant association with lymph-node metastasis. CONCLUSIONS: The results suggest that MUC6 is expressed in normal colorectal tissues and tumors, that MUC6 expression is especially strong in mucinous carcinomas, and that MUC2 expression is associated with lymph-node metastasis, among the prognostic factors.

A Case of Multiple Hyperplastic Polyps in the Stomach and Colorectum / 대한소화기내시경학회지

Hyperplastic polyps are a benign epithelial proliferation and a common type of colorectal and gastric polyps. Malignant change of hyperplatic polyps is rare. Patients with multiple lesions however, tend to have a high frequency of malignancy. Colorectal polyposis syndromes with gastric polyps include familial adenomatous polyposis, Gardners syndrome, Peutz-Jeghers syndrome, juvenile polyposis and others. But the case of colorectal hyperplastic polyposis with multiple gastric hyperplastic polyps has not been reported until now. A case was recently experienced involving a 32 year old women with both colorectal and gastric hyperplastic polyposis. Multiple hyperplastic polyps were found in the lower part of the body and the antrum of the stomach, rectosigmoid, transverse and ascending colon.

Histopathological study of colorectal injury after endoscopic polypectomy / 中华消化内镜杂志

Objective The study was attempted to observe the colorectal injury due to endoscopic snare polypectomy. Methods Histopathological study was conducted on 47 snared colorectal polyps as well as on the corresponding sites in 34 patients who underwent surgery thereafter for malignancy. Results The injury to all snared specimens was confined within submucosa,while that to surgically resected specimens at the snared sites extended to muscular and serosal layers in 28 out of 34 cases, which manifested as focal necrosis in inner muscularis and hemorrhage between inner and outer muscle layers, bearing no continuity with submucosal change.The mean size of polyps snared with injury to muscularis and serosa at the site was larger than those without ( P10mm.

Prognostic Implications of DNA Ploidy and S-phase Fraction Comparing with Other Prognostic Factors in Advanced Coloretal Adenocarcinomas

Dukes' stage of colorectal carcinoma has proven to be the most reliable and conventional prognostic indicator, followed by histological grade, lymph node metastases, tumor size, vascular and neural invasion. Flow cytometric analysis of DNA ploidy and S-phase fraciion (SPF) was examined to elucidate the correlations between sex, age, preoperative serum carcinoembryonic antigen (CEA) value, Dukes' stage, tumor site, size, gross features, histologic grade, and survival rate in 117 paraffin-embedded tissues of 68 cases of colorectal adenocarcinoma in Dukes' stage and 39 cases of colorectal adenoma and 10 cases of normal colonic mucosa. DNA aneuploidy was detected in 30 cases(44%) in adenocarcinomas and 6 cases (15%) in adenomas. Although the DNA ploidy and SPF did not show any correlation with sex, age, preoperative serum CEA level, Dukes' stage, tumor size, site and gross features, the incidence of DNA aneuploidy in the moderately differentiated adenocarcinomas was significantly higher than that of the well differentiated adenocarcinomas (p=0.0127) An apparent correlation was found between survival rate and DNA ploidy, Dukes' stage, histologic grade and preoperative serum CEA value. Dukes' stage was the most reliable prognostic indicator (p=0.0106), followed by histologic grade (p=0.0230), DNA aneuploidy (p=0.0251) and preoperative serum CEA level. (p=0.0369) In the patients with Dukes' stage C, DNA aneuploidy was more important than histologic grade as a prognostic indicator (p=0.0202). Although high SPF, greater than 21% in adenocarcinoma, was associated with the lower 5-year survival rate (12.0%), it was not statistically significant. These results suggest that DNA aneuploidy is regarded as biologic aggressiveness and considered as independent and/or dependent prognostic indicator along with Dukes' stage. However, prognostic utility of the SPF was not significant.